Identification of Two Lpp20 CD4+ T Cell Epitopes in Helicobacter pylori-Infected Subjects

Abstract

Antigen-specific CD4+ T cells play an essential role in effective immunity against Helicobacter pylori (H. pylori) infection. Lpp20, a conserved lipoprotein of H. pylori, has been investigated as one of major protective antigens for vaccination strategies. Our previous study identified two H-2d-restricted CD4+ T cell epitopes within Lpp20 and an epitope vaccine based on these epitopes was constructed, which protected mice in prophylactic and therapeutic vaccination against H. pylori infection. Immunodominant CD4+ T cell response is an important feature of antiviral, antibacterial, and antitumor cellular immunity. However, while many immunodominant HLA-restricted CD4+ T cell epitopes of H. pylori protective antigens have been identified, immunodominant HLA-restricted Lpp20 CD4+ T cell epitope has not been elucidated. In this study, a systematic method was used to comprehensively evaluate the immunodominant Lpp20-specific CD4+ T cell response in H. pylori-infected patients. Using in vitro recombinant Lpp20 (rLpp20)-specific expanded T cell lines from H. pylori-infected subjects and 27 18mer overlapping synthetic peptides spanned the whole Lpp20 protein, we have shown that L55–72 and L79–96 harbored dominant epitopes for CD4+ T cell responses. Then the core sequence within these two 18mer dominant epitopes was screened by various extended or truncated 13mer peptides. The immunodominant epitope was mapped to L57–69 and L83–95. Various Epstein-Barr virus (EBV) transformed B lymphoblastoid cell lines (B-LCLs) with different HLA alleles were used as antigen presenting cell (APC) to present peptides to CD4+ T cells. The restriction molecules were determined by HLA class-antibody blocking. L57–69 was restricted by DRB1-1501 and L83–95 by DRB1-1602. The epitopes were recognized on autologous dendritic cells (DCs) loaded with rLpp20 but also those pulsed with whole cell lysates of H. pylori (HP-WCL), suggesting that these epitopes are naturally processed and presented by APC. CD4+ T cells were isolated from H. pylori-infected patients and stimulated with L57–69 and L83–95. These two epitopes were able to stimulate CD4+ T cell proliferation. This study may be of value for the future development of potential H. pylori vaccine.

Notch 1 Is Involved in CD4+ T Cell Differentiation Into Th1 Subtype During Helicobacter pylori Infection

“…A similar predominant Th1 response was observed early in rhesus macaques during acute H. pylori infection (Mattapallil et al, 2000). Several research groups including our team demonstrated that immunodominant CD4 + epitopes of some H. pylori antigens induced a Th1-skewed response in humans (Chen et al, 2013;Yang et al, 2013;Ning et al, 2018). Taken together, these results highlight a vigorous Th1 immune response against H. pylori infection.…”

Review: Helicobacter: Inflammation, immunology, and vaccines

“…The highly conserved H pylori Lpp20 lipoprotein was previously shown to induce protection against H pylori infection in mice. 31 Ning et al 32 identified two immunodominant epitopes within H pylori Lpp20 that were able to stimulate the proliferation of CD4 + T cells from H pylori-infected subjects. Whether these epitopes confer protective immunity is, however, unclear.…”

Urolithin A Attenuates Helicobacter pylori-Induced Damage In Vivo

“…HP-IgG-Ab is an immunoglobulin which can be used to diagnose H. pylori infection. , It could be seen from Figure that the content of HP-IgG-Ab of Group HP was statistically significant higher compared with that of Group C. This revealed that H. pylori induced the secretion of IgG-Ab antibodies.…”